Altenrative Forms Of The Phosphodeisterase -4 Inhibitor N-Cyclopropyl-1- -3{3-[(1-Oxidopyryidin-3-Yl) Phenyl]-4-Oxo-1,4-Dihydro-1,8-Naphthyridine-3-Carboxyamide

Abstract

The present invention is directed to alternative forms of the title phosphodiesterase 4 inhibitor which has the structural formula shown immediately below: Compound IX

1 . The compound IX 
       
         
           
           
               
               
           
         
       
       which is designated Form I. 
     
     
         2 . The Form I, the compound IX, according to  claim 1 , wherein the Form I has characteristic reflection peaks at 4.5, 9.2, 9.9, 10.9, and 13.6 degrees 20 determined by x-ray powder diffraction. 
     
     
         3 . The hemihydrate and dehydrated dihydrate of the compound IX 
       
         
           
           
               
               
           
         
       
       Which is designated Form II. 
     
     
         4 . The Form II, the hemihydrate and dehydrated dihydrate of the compound IX, according to  claim 3 , wherein the Form I has characteristic reflection peaks at 7.1, 8.6, 10.6, and 17.1 degrees 20 determined by x-ray powder diffraction. 
     
     
         5 . The monohydrate of the compound IX 
       
         
           
           
               
               
           
         
       
       which is designated Form III. 
     
     
         6 . The Form III, the monohydrate of the compound IX, according to  claim 5 , wherein the Form III has characteristic reflection peaks at 8.5, 13.2, 14.7, and 15.8 degrees 20 determined by x-ray powder diffraction. 
     
     
         7 . The tetrahydrate of the compound IX 
       
         
           
           
               
               
           
         
       
       which is designated Form IV. 
     
     
         8 . The Form IV, the tetrahydrate of the compound IX, according to  claim 7 , wherein the Form IV has characteristic reflection peaks at 6.5, 7.7, 8.8, and 13.0 degrees 20 determined by x-ray powder diffraction. 
     
     
         9 . The dihydrate of the compound IX 
       
         
           
           
               
               
           
         
       
       which is designated Form V. 
     
     
         10 . The Form V, the dihydrate of the compound IX, according to  claim 9 , wherein the Form V has characteristic reflection peaks at 6.9, 12.6, 14.0, and 17.4 degrees 20 determined by x-ray powder diffraction. 
     
     
         11 . A composition comprising Form I and Form II of the compound IX 
       
         
           
           
               
               
           
         
       
     
     
         12 . A composition according to  claim 11 , wherein the ratio of Form I to Form II is at least 10:1 by weight. 
     
     
         13 . A composition according to  claim 12 , wherein the ratio of Form I to Form II is at least 20:1 by weight. 
     
     
         14 . A composition according to  claim 13 , wherein the ratio of Form I to Form II is from about 20:1 to about 200:1 by weight. 
     
     
         15 . A composition comprising an aqueous solution or suspension of Form IV, the tetrahydrate of the compound IX. 
     
     
         16 . A pharmaceutical composition comprising a non-toxic therapeutic amount of a Form I according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         17 . A pharmaceutical composition comprising a non-toxic therapeutic amount of a Form I according to  claim 3  and a pharmaceutically acceptable carrier. 
     
     
         18 . A pharmaceutical composition comprising a non-toxic therapeutic amount of a Form III, the monohydrate, according to  claim 5  and a pharmaceutically acceptable carrier. 
     
     
         19 . A pharmaceutical composition comprising a nontoxic therapeutic amount of a Form IV, the tetrahydrate, according to  claim 7  and a pharmaceutically acceptable carrier. 
     
     
         20 . A pharmaceutical composition comprising a non-toxic therapeutic amount of a Form V, the dihydrate, according to  claim 9  and a pharmaceutically acceptable carrier. 
     
     
         21 . The hemihydrate of the compound IX 
       
         
           
           
               
               
           
         
       
       which is designated Form VI. 
     
     
         22 . The Form VI, a hemihydrate of the compound IX, according to  claim 21 , wherein the Form VI has characteristic reflection peaks at 6.0, 15.3, 15.9, 23.8 and 25.0 degrees 20 determined by x-ray powder diffraction. 
     
     
         23 . A composition comprising Form I and Form VI of the compound IX 
       
         
           
           
               
               
           
         
       
     
     
         24 . A composition according to  claim 23 , wherein the ratio of Form I to Form VI is at least 10:1 by weight. 
     
     
         25 . A composition according to  claim 24 , wherein the ratio of Form I to Form VI is at least 20:1 by weight. 
     
     
         26 . A pharmaceutical composition comprising a non-toxic therapeutic amount of a Form VI, the hemihydrate, according to  claim 21  and a pharmaceutically acceptable carrier. 
     
     
         27 . The anhydrate of the compound IX 
       
         
           
           
               
               
           
         
       
       which is designated Form VII. 
     
     
         28 . The Form VII, an anhydrate of the compound IX, according to  claim 27 , wherein the Form VII has characteristic reflection peaks at 14.0, 17.4, 25.2, and 28.1 degrees 20 determined by x-ray powder diffraction.